New guidelines for the pharmacological treatment of heart failure have suggested patients with reduced ejection fraction (HFrEF ) should be on the “big four” therapies as soon as possible after diagnosis.

A consensus statement (link) published in the MJA has updated 2018 guidelines, broadening the scope of angiotensin receptor neprilysin inhibitor (sacubitril–valsartan) use and SGLT2 inhibitors.

The Evidence to Practice group, led by Professor Andrew Sindone, Associate Professor Carmine de Pasquale and Professor John Atherton, has recommended increased use of SGLT2 inhibitors and a mineralocorticoid receptor antagonist (finerenone) in certain instances for people with type 2 diabetes.

“Heart failure prevention remains a major health priority, with recent studies reporting that SGLT2 inhibitors and mineralocorticoid receptor antagonist (MRA) can prevent or delay the development of heart failure in patients with diabetic kidney disease,” the statement said.

“In patients with established HFrEF, there is now strong evidence to support combining either an angiotensin receptor neprilysin inhibitor or angiotensin-converting enzyme (ACE) inhibitor with a beta blocker, MRA and SGLT2 inhibitor in all patients.”

Professor Sindone, from the Concord Hospital and the University of Sydney, told the limbic that was among the most significant changes for cardiology clinics.

“All patients with [heart failure with reduced ejection fraction] HFrEF should be on the ‘big four’ of ARNI/ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor as soon as possible,” he said.

Further, he said the early initiation of ARNIs should be undertaken rather than waiting three months and repeating echocardiograms. For patients who have congestion and HFpEF, he recommended the early use of SGLT2 inhibitors.

Professor Sindone said the delay in treating patients with HFrEF remained evidence-practice gap, saying “very few” were taking all the four guideline-directed medical therapy agents.

“Implementing these changes in a newly diagnosed HFrEF patient at age 55 vs 2013 therapy of ACE inhibitor + beta-blocker would add an extra 6.9 years of life and reduce readmission to hospital by 60%,” he said.

Likewise, Royal Brisbane and Women’s Hospital and the University of Queensland’s Professor Atherton, said the most important changes involved recognising, “the benefit of introducing all four major treatment approaches in patients with HFrEF, as opposed to taking a sequential approach”.

Further, he said the second major change was to consider an SGLT2 inhibitor (empagliflozin) for patients with HFpEF, but this remained before the TGA and PBS for approval and consideration.

Limitations with PBS listings were leading to the under-utilisation of some treatments, Prof Atherton said, such as sacubitril-valsartan in de novo HFrEF.

Professor Sindone agreed, saying the use of SGLT2 inhibitors for HFpEF was based on the EMPEROR Preserved study, while ARNIs for HFrEF showed a benefit in the PIONEER-HF and TRANSITION trials.

“We are hoping that the TGA and Pharmaceutical Benefits Advisory Committee [PBAC] will recognise these benefits and approve these agents for these indications as they are evidence based and will improve survival and reduce heart failure hospitalisations.”

Heart failure is a significant challenge in Australia. More than 100,000 people have self-reported the condition, but this is believed to be an underestimate of the true prevalence.

Evidence to Practice’s main recommendations for the pharmacological management of heart failure:

• Use of SGLT2 inhibitors to prevent hospitalisation for heart failure in type 2 diabetes mellitus can be extended to patients with multiple cardiovascular risk factors, albuminuric chronic kidney disease, or atherosclerotic cardiovascular disease
• New evidence supports the use of a mineralocorticoid receptor antagonist (finerenone) to prevent heart failure in type 2 diabetes mellitus associated with albuminuric chronic kidney disease
• In addition to renin angiotensin system inhibitors (angiotensin receptor neprilysin inhibitor preferred), beta blockers and mineralocorticoid receptor antagonists, an SGLT2 inhibitor (dapagliflozin or empagliflozin) is recommended in all patients with heart failure with reduced left ventricular ejection fraction (LVEF ≤ 40%) (HFrEF). Lower quality evidence supports these therapies in patients with heart failure with mildly reduced LVEF (41-49%) (HFmrEF)
• A soluble guanylate cyclase stimulator (vericiguat), selective cardiac myosin activator (omecamtiv mecarbil) and, if iron deficient, intravenous iron (ferric carboxymaltose) provide additional benefits in persistent HFrEF
• An SGLT2 inhibitor (empagliflozin) should be considered in patients with heart failure with preserved LVEF (≥ 50%) (HFpEF).

The authors said they were motivated to develop a consensus statement for heart failure because there have been a number of clinical trials evaluating novel therapies since the 2018  National Heart Foundation of Australia (NHFA) and Cardiac Society of Australia and New Zealand (CSANZ) heart failure guidelines were released. These were not scheduled for review and since there was a high level of clinician interest, the Evidence to Practice academic group reviewed the most recent studies evaluating new and established drugs to prevent or treat heart failure.

The group was supported by the South Australian Health and Medical Research Institute (SAHMRI) and no other funding was provided apart from an honorarium offered to attend the virtual meeting by the Evidence to Practice Group.